Sitagliptin Does Not Increase Heart Failure Risk for Patients With T2D

Recently, clinical trials of dipeptidyl peptidase 4 (DPP4) inhibitor use have suggested the medications may be associated with an increased risk of hospitalization for heart failure in people with type 2 diabetes (eg, the SAVOR-TIMI 53 trial of sitagliptin). Meta-analyses of these and other DPP4 medications suggested the agents may be associated with an up to 25% increased risk for heart failure hospitalization.

Now secondary analysis of data from the TECOS (Trial Evaluating Cardiovascular Outcomes with Sitagliptin) trial of sitagliptin finds that the drug does not affect the risk for heart failure hospitalization or related adverse clinical outcomes in people with type 2 diabetes, both overall and among high-risk subgroups of patients. The new analysis provides further support that sitagliptin may be safely used in a population of patients with type 2 diabetes at high cardiovascular risk.

Darren K. McGuire, MD, MHsc, of the University of Texas Southwestern Medical Center, Dallas, and colleagues involved in the TECOS trial followed 14,671 adults with type 2 diabetes and prevalent atherosclerotic vascular disease. The mean age of the study subjects was 50 years and older and they had a baseline glycated hemoglobin level (A1C) of 6.5% to 8% on stable antihyperglycemic medication. Among 2643 patients with previous heart failure at trial entry, 1303 were assigned to receive sitagliptin and 1340 to placebo, in addition to standard care.

Over a mean follow-up of 2.9 years, there were no significant differences between sitagliptin versus placebo for the risk of hospitalization for heart failure (3.1% versus 3.1%, respectively) or for the composite of hospitalization for heart failure or cardiovascular death (7.3% versus 7.2%, respectively). Post-hospitalization heart failure all-cause death was similar in the sitagliptin and placebo groups (29.8% vs 28.8%, respectively), as was cardiovascular death (22.4% vs 23.1%, respectively).

The investigators caution that the study has certain limitations and that the findings should be interpreted carefully because TECOS included patients with well-controlled glucose levels and excluded patients with kidney dysfunction. Thus, the observations may not apply to patients with these issues. However, no increased risk was observed with sitagliptin use among patients with baseline mild or moderate kidney impairment, they point out.

The study was published in JAMA Cardiology. An accompanying editorial by Benjamin M. Scirica, MD, MPH, noted that no class of diabetes drugs has been as thoroughly evaluated as the DPP4 inhibitors.

“Overall, they are safe without any increase in cardiovascular death, myocardial infarction, or stroke,” he wrote. “Of the three DPP4 inhibitors, sitagliptin appears to have the safest cardiovascular profile.”

He pointed out that these trials also highlight the importance of well-powered trials with hard clinical end points. Without such trials, we would not have detected a potential heart failure risk with saxagliptin and might have been left with the impression that the DPP4 class was cardioprotective.

“In fact,” Scirica wrote, “and despite preclinical data, there does not appear to be any nonglycemic-mediated cardioprotection.”

TECOS was funded by Merck Sharp & Dohme.